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T Corrah

Publications and source records attributed to T Corrah.

At least 19 recordsLinked to original sources
PubMed2005

Mycobacterium tuberculosis genome-wide screen exposes multiple CD8 T cell epitopes.

Mounting evidence suggests human leucocyte antigen (HLA) class I-restricted CD8(+) T cells play a role in protective immunity against tuberculosis yet relatively few epitopes specific for the causative organism, Mycobacterium tuberculosis, are reported. Here a total genome-wide screen of M. tuberculosis was used to identify putative HLA-B*3501 T cell epitopes. Of 479 predicted epitopes, 13 with the highest score were synthesized and used to restimulate lymphocytes from naturally exposed HLA-B*3501 healthy individuals in cultured and ex vivo enzyme-linked immunospot (ELISPOT) assays for interferon (IFN)-gamma. All 13 peptides elicited a response that varied considerably between individuals. For three peptides CD8(+) T cell lines were expanded and four of the 13 were recognized permissively through the HLA-B7 supertype family. Although further testing is required we show the genome-wide screen to be feasible for the identification of unknown mycobacterial antigens involved in immunity against natural infection. While the mechanisms of protective immunity against M. tuberculosis infection remain unclear, conventional class I-restricted CD8(+) T cell responses appear to be widespread throughout the genome.

CD8-Positive T-Lymphocytes↗
PubMed2003

Surveillance of drug-resistant Mycobacterium tuberculosis in The Gambia.

To determine the rates of drug-resistant tuberculosis in The Gambia, Mycobacterium tuberculosis isolates obtained from 225 patients during a nationwide survey were tested against isoniazid, rifampicin, ethambutol and streptomycin using the resistance ratio method. Only nine (4%) of the patients had strains that were resistant to one or more drugs. None of the patients with drug-resistant M. tuberculosis had previously been treated for tuberculosis. Drug-resistant tuberculosis is, as yet, not common in The Gambia. Periodic surveys for drug-resistant tuberculosis are recommended to monitor changes that may emerge over time.

Adolescent↗
PubMed2003

Clinical and radiological presentation of 340 adults with smear-positive tuberculosis in The Gambia.

SETTING: Four clinics in The Gambia. OBJECTIVE: To document clinical and radiographic presentations of sputum smear-positive tuberculosis in adults. DESIGN: Newly diagnosed acid-fast bacilli (AFB) smear, culture-positive tuberculosis patients aged > or = 15 years were interviewed and examined, and underwent tuberculin skin testing, HIV testing and chest X-ray reviewed by a chest physician using set criteria. RESULTS: Of 340 patients enrolled (median age 29 years; males 73%), 8.3% were HIV-positive. One-third reported haemoptysis, > 90% reported weight loss and fever, and wasting was the most common sign (69%). Crepitations were the most frequent auscultatory finding (41%). The most common radiological lesion was a patchy infiltrate (> 90%). Cavitation was present in 206 patients (60.6%), most frequently occurred in the upper lung fields, was associated with increasing bacterial load in the sputum, and was less prevalent in HIV-positive patients (45% vs. 62%; P = 0.07). Auscultatory and chest X-ray findings matched only one-third of the time. CONCLUSION: In our setting, wasting is the most common clinical sign of sputum smear-positive tuberculosis. Auscultatory findings correlate poorly with radiological abnormalities. Cavitation is associated with increasing bacterial load in the sputum, and is therefore a strong indicator for early treatment.

Adolescent↗
PubMed2003

Determinants of prognosis among black Africans with hypertensive heart failure.

One hundred and seven consecutive Black Africans hypertensive heart failure patients made of 52 Gambians and 55 Nigerians (51 males + 56 females) aged 53.6 +/- 12.1 years were followed-up for 12 months or till death. One-year survival curve was determined using Kaplan-Meiers method. The survivors and the deceased were compared using univariate and multivariate analysis. Mean blood pressures were 180.4 +/- 28.2 mmHg (range: 130-250 mmHg) systolic and 117.0 +/- 12.9 mmHg (range: 100-160 mmHg) diastolic. Duration of hypertension ranged from 0.5 to 23 years. The rate of undetected hypertension was 44%. Overall one-year survival rate was 71%. Twenty two percent of deaths occurred within the first 3 months of HHF. One-year survival rate among the survivors of this period was 89.4%. A strong negative correlation existed between cumulative survival and the duration of heart failure (y = 0.9812, x(2) = 0.1173, R = 0.965). Compared to the survivors, the deceased had significantly higher systolic blood pressure (191.9 +/- 32.2 mmHg versus 175.1 +/- 25.2 mmHg; P < 0.05), diastolic blood pressure (123.7 +/- 15.8mmHg versus 114.3 +/- 10.3 mmHg; P < 0.05), cardiothoracic index (69.2 +/- 3.9% versus 66.2 +/- 4.2%; P < 0.05) and serum creatinine (148.6 +/- 42.2 umol/L versus 113.8 +/- 36.4 umol/L; P < 0.05). Compared to the patients aged 40 or more years, patients aged below 40 years had significantly lower one-year survival rate (41.7% versus 74.1%; P < 0.05). One-year survival rate was significantly higher among patients on captopril medication than those without (75% versus 52.6%; P < 0.05). However, only serum creatinine had statistically differing values between the deceased and survivors (df = 1 SS = 10272, F = 7.60, p = 0.007). Basic clinical and biochemical parameters could therefore be useful prognostic markers in hypertensive heart failure.

Analysis of Variance↗
PubMed2001

Tuberculosis contacts but not patients have higher gamma interferon responses to ESAT-6 than do community controls in The Gambia.

The Mycobacterium tuberculosis antigen ESAT-6 has been proposed for tuberculosis immunodiagnosis. In The Gambia, 30% of community controls produced gamma interferon (IFN-gamma) in response to ESAT-6. Increased proportions of responders and intensities of responses were found in household contacts. Responses that were initially low in tuberculosis patients increased after treatment. An ESAT-6 IFN-gamma assay will be of limited use in the diagnosis of tuberculosis in countries where tuberculosis is endemic. Its role in contact tracing should be evaluated further.

Adolescent↗
PubMed2001

Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12.

The T helper (Th) 1/Th2 balance in the T-lymphocyte response to purified protein derivative (PPD) was evaluated at the clonal level in six Italian and five Gambian patients with pulmonary tuberculosis (TB) before and after antimycobacterial therapy, as well as in five Gambian and four Italian healthy immune control subjects. In untreated patients, most PPD-specific clones derived from either peripheral blood or pleural effusions showed a Th0 cytokine profile (production of both interferon [IFN]-gamma and interleukin [IL]-4/IL-5). After 6 mo of therapy and clinical healing, most PPD-specific clones showed a polarized Th1 profile (production of IFN-gamma but not IL-4/IL-5) in both Italian and Gambian patients. The Th1 polarization was less marked in Gambian than in Italian patients and failed to occur in another group of four Italian patients who experienced treatment failure. The cytokine profile observed after successful therapy in patients with TB was similar to that found in healthy control subjects. T-cell clones of undefined specificity generated from PPD-stimulated cultures showed a similar Th0/Th2 bias in Gambian individuals and Italian patients with treatment failure. The Th0/Th2-biased responses in Gambian patients before therapy could be modulated in vitro by IFN-alpha or IL-12, which induced a Th1 polarization of both PPD-specific and bystander T cells. Our data show that active TB associates with a predominant Th0 response to mycobacterial antigens that could play a role in the pathogenesis of the disease. Adjunctive immunotherapy using Th1-polarizing cytokines could increase host defense against mycobacteria and accelerate healing.

Adult↗
PubMed2000

Genetic susceptibility to tuberculosis in Africans: a genome-wide scan.

Human genetic variation is an important determinant of the outcome of infection with Mycobacterium tuberculosis. We have conducted a two-stage genome-wide linkage study to search for regions of the human genome containing tuberculosis-susceptibility genes. This approach uses sibpair families that contain two full siblings who have both been affected by clinical tuberculosis. For any chromosomal region containing a major tuberculosis-susceptibility gene, affected sibpairs inherit the same parental alleles more often than expected by chance. In the first round of the screen, 299 highly informative genetic markers, spanning the entire human genome, were typed in 92 sibpairs from The Gambia and South Africa. Seven chromosomal regions that showed provisional evidence of coinheritance with clinical tuberculosis were identified. To identify whether any of these regions contained a potential tuberculosis-susceptibility gene, 22 markers from these regions were genotyped in a second set of 81 sibpairs from the same countries. Markers on chromosomes 15q and Xq showed suggestive evidence of linkage (lod = 2.00 and 1.77, respectively) to tuberculosis. The potential identification of susceptibility loci on both chromosomes 15q and Xq was supported by an independent analysis designated common ancestry using microsatellite mapping. These results indicate that genome-wide linkage analysis can contribute to the mapping and identification of major genes for multifactorial infectious diseases of humans. An X chromosome susceptibility gene may contribute to the excess of males with tuberculosis observed in many different populations.

Adolescent↗
PubMed2000

Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa.

OBJECTIVE: To examine whether the levels of plasma RNA and DNA provirus predict the rate of CD4 cell decline and patient death. DESIGN: Retrospective analysis of HIV-2 cohort subjects. METHODS: Fifty-two subjects were recruited between January 1991 and December 1992. HIV-2 RNA levels in plasma and DNA levels in peripheral blood mononuclear cells (PBMC) were measured using in-house quantitative PCR assays. The annual rate of CD4 cell decline was calculated using the least-squares method. The survival data on 31 December 1997 were used. RESULTS: The mean percentage of CD4 cells at baseline was 30.7 (SD, 9.5). In a linear regression model, the annual rate of CD4 cell decline was 1.76 CD4% faster for every increase in one log10 RNA copies/ml [95% confidence interval (CI), 0.81-2.7; P = 0.0006; r = 0.46; n = 52] and 1.76 CD4% faster for every increase in log10 DNA copies/10(5) PBMC (95% CI 0.46-3.1; P = 0.01; r = 0.33; n = 42). In a multiple linear regression model, RNA load was related to CD4 decline independently of DNA load (P = 0.02). The overall mortality rate was 7.29/100 person-years. In a Cox regression model, the hazard rate increased by 2.12 for each log10 increase in RNA load (95% CI, 1.3-3.5; P = 0.0023) but only by 1.09 for each log10 increase in DNA load (95% CI, 0.64-1.87; P = 0.8). CONCLUSION: This longitudinal study shows for the first time that a baseline HIV-2 RNA load predicts the rate of disease progression. HIV-2-infected patients with a high viral load may need to be treated as vigorously as HIV-1 patients.

Adolescent↗
PubMed2000

Prior BCG vaccination improves survival of Gambian patients treated for pulmonary tuberculosis.

The protection provided by BCG against pulmonary tuberculosis ranges from nil to over 90%. While BCG protects against the more serious forms of tuberculosis, it is not known whether or not it protects patients with pulmonary tuberculosis from death. In a study designed to look at the effects of immunotherapy with M. vaccae as an adjunct to chemotherapy in 285 adult Gambian patients treated for proven pulmonary tuberculosis, we examined the association between the presence or absence of a BCG scar and mortality. The data showed that subjects who had a BCG scar were significantly younger than those who did not, and were less likely to have nutritional oedema. During the course of treatment, none of the 85 patients who had a BCG scar died compared to 35 of 200 patients (17.5%) who did not (P < 0.001). In these Gambian patients with pulmonary tuberculosis, prior vaccination with BCG may have provided substantial protection against death. However, there is the possibility that this finding is the result of confounding by other factors or has arisen from bias. Researchers with similar data need to investigate this question as this association, if true, could have major implications for BCG vaccination.

Adolescent↗
PubMed2000

A longitudinal study of in vitro IFNgamma production and cytotoxic T cell responses of tuberculosis patients in the gambia.

SETTING: This study was carried out at the MRC Laboratories, The Gambia. OBJECTIVES: To characterize the antigen-specific IFNgamma production and cytotoxic T cell (CTL) responses of patients during active tuberculosis, treatment, and following recovery. DESIGN: PBMC were isolated from 37 patients with tuberculosis and incubated with either PPD, live M. bovis BCG, or no antigen and IFNgamma production measured after 7 days. CTL activity against these antigens was determined using autologous antigen-pulsed monocyte-derived macrophages as target cells. A subset of these patients (7-18 depending on antigen and assey used) were tested 2 months into drug treatment and 3 months after discharge. A group of blood bank donors (n= 21) were also tested to evaluate IFNgamma responses in endemic controls; a subset (n= 16) were also tested for CTL activity. RESULTS: The ability to produce IFNgamma in response to mycobacterial antigens correlated with the Mantoux skin test status of the patient. IFNgamma production to live M. bovis BCG was diminished at diagnosis but returned after 2 months of drug treatment, and was sustained after completion of drug therapy. The CTL responses to both PPD and live M. bovis BCG were reduced during the period of drug treatment compared to those at diagnosis, but returned to the original levels after recovery. CONCLUSIONS: Drug treatment induced marked alterations in the immune responses of tuberculosis patients with induction of IFNgamma production in response to stimulation with live M. bovis BCG. This may indicate activation of both CD4 and CD8 T cells.

Adolescent↗
PubMed1999

Newborns develop a Th1-type immune response to Mycobacterium bovis bacillus Calmette-Guérin vaccination.

Data obtained in animals indicate that neonatal immune responses are biased toward Th2. This could reduce the efficacy of vaccines against viral and mycobacterial diseases. The ability of human newborns to develop a Th1 immune response upon immunization has not been studied. Since the vaccine Mycobacterium bovis bacillus Calmette-Guérin (BCG) triggers a Th1-type response in adults, we investigated whether it induces a similar response in newborns and whether age at vaccination influences immunogenicity. We found that BCG vaccination at birth induces a memory Th1-type response of similar magnitude to that when given later in life. This study demonstrates that human newborns can be immunized against pathogens controlled by a Th1 immune response.

Antigens, Bacterial↗
PubMed1999

Proviral load and immune function in blood and lymph node during HIV-1 and HIV-2 infection.

Proviral load as well as lymphocyte phenotype and function were compared in peripheral blood and lymph node compartments of 17 HIV-1, 12 HIV-2 and three dually infected patients with lymphadenopathy. The mean percentage (95% confidence interval (CI)) of CD4+ cells was higher in lymph node mononuclear cells (LNMC) than in peripheral blood mononuclear cells (PBMC) in both infections, being 26.7% (21. 1%, 32.3%) and 15.3% (10.4%, 20.2%), respectively, for HIV-1-infected patients (P = 0.0001) and 32.3% (22.7%, 41.9%) and 22. 1% (13.6%, 30.6%), respectively, for HIV-2-infected patients (P = 0. 02). In both types of infection, proviral load adjusted for number of CD4+ cells was higher in LNMC than in PBMC: the geometric mean (95% CI) was 8937 (4991; 16 003) and 4384 (2260; 8503), respectively, for HIV-1 patients (P = 0.02) and 1624 (382; 6898) and 551 (147; 2058) DNA copies, respectively, for HIV-2 patients (P = 0.05). Proviral load in both compartments was closely correlated (HIV-1, r = 0.60, P = 0.01; and HIV-2, r = 0.83, P = 0.0003). In both infections, proliferation and interferon-gamma (IFN-gamma) production in response to purified protein derivative (PPD) was lower in LNMC than in PBMC, both of which, in turn, were lower than in healthy controls. These results indicate that in HIV-2 as in HIV-1 infection, infected cells have a tropism for the lymph nodes resulting in higher viral load in this compartment and lower lymphocyte responses to the recall antigen PPD which may increase susceptibility to tuberculosis.

Adult↗
PubMed1999

Retinal manifestations of HIV-1 and HIV-2 infections among hospital patients in The Gambia, west Africa.

BACKGROUND: In developed countries, 50-75% of AIDS patients develop retinal complications and about 20-40% acquire cytomegalavirus (CMV) retinitis. We conducted a cross-sectional survey to determine prevalence of these in The Gambia where both HIV-1 and HIV-2 infection are present and the prevalence of HIV-1 is rising. METHOD: All patients attending hospital whose percentage CD4+ cells (CD4%) was below 14, the level associated typically with an AIDS diagnosis, and one half of those whose CD4% was 14 or above were asked to join the study. Fifty-six HIV-1, 52 HIV-2 and 12 dually infected patients were recruited. Photographs of the fundi were taken and interpreted independently. The findings were related to the patients' percentage CD4+ cells. RESULTS: The CD4% was < 14 in 40 patients and < 7 in 17 patients. Thirty-six patients were male. No cases of CMV retinitis were found. Four patients whose CD4% were 4, 5, 11 and 23 had cotton wool spots ranging in number from 1 to 14 for any one patient. The prevalence of cotton wool spots was 8% (95% CI, 0-16%) among patients with CD4% below 14 and 12% (95% CI, 0-27) among patients with CD4% below 7. One of the 4 patients had associated microaneurysm and blot haemorrhages typical of more advanced HIV microvasculopathy. CONCLUSION: CMV retinitis is less common in The Gambia than in developed countries. Non-infectious retinopathy may also be less common.

AIDS-Related Opportunistic Infections↗
PubMed1999

Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene.

The active metabolite of vitamin D, 1,25 dihydroxyvitamin D3, is an important immunoregulatory hormone [1]. Its effects are exerted by interaction with the vitamin D receptor, which is present on human monocytes and activated T and B lymphocytes. Variation in the vitamin D receptor gene was typed in 2015 subjects from large case-control studies of three major infectious diseases: tuberculosis, malaria, and hepatitis B virus. Homozygotes for a polymorphism at codon 352 (genotype tt) were significantly underrepresented among those with tuberculosis (chi2=6.22, 1 df, P=. 01) and persistent hepatitis B infection (chi2=6.25, 1 df, P=.01) but not in subjects with clinical malaria compared with the other genotypes. Therefore, this genetic variant, which predisposes to low bone mineral density in many populations, may confer resistance to certain infectious diseases.

Adolescent↗